Felodipine and renal function in lung transplantation: A randomized placebo-controlled trial.

BACKGROUND: Calcium channel blockers may ameliorate the decline in renal function caused by calcineurin inhibitors in lung transplantation (LTX) recipients. We hypothesized that pre-operative and 12-week post-operative treatment with the calcium channel blocker felodipine would reduce the decline in glomerular filtration rate (GFR). METHODS: In this prospective, randomized, double-blind trial, 39 LTX recipients were transplanted and received placebo (n = 19; GFR, 102 ml/min/1.73 m2 [range, 91-113 ml/min/1.73 m2]) or felodipine (n = 20, GFR, 96 ml/min/1.73 m2 [range, 88-104 ml/min/1.73 m2]). Pre-operative treatment was titrated post-operatively to 10 mg or the maximum tolerable dose. The primary end-point was the change in GFR using Cr-51-labeled EDTA from LTX to 12 weeks thereafter, and follow-up was 52 weeks. RESULTS: The treatment group showed an absolute mean decline in GFR of 31 ml/min/1.73 m2 (95% CI: -40 to 22 ml/min/1.73 m2), whereas that of the placebo group was 48 ml/min/1.73 m2 (95% confidence interval [CI]: -56 to 40 ml/min/1.73 m2). Thus, the difference between groups at 12 weeks was 17 ml/min/1.73 m2 (95% CI: 4-29 ml/min/1.73 m2; p = 0.01). Half of the patients were unable to complete the 3-month primary follow-up, and the analysis includes these patients by intention-to-treat. After 52 weeks (40 weeks after termination of treatment), the treatment effect was maintained at 12 ml/min/1.73 m2 (95% CI: 0-24 ml/min/1.73 m2, p = 0.05). The number of days with registered hypotension was significantly higher in the felodipine group than in the placebo group (39 days vs 13 days, rate ratio: 2.9 [95% CI: 1.5-5.3]). CONCLUSIONS: Use of felodipine in select patients was associated with greater preservation in renal function early (90 days) after LTX. The observed benefits were attenuated by 1 year, although trends in better renal function were noted.

Meta-analysis of routine blood tests as predictors of mortality in COPD.

OBJECTIVE: The purpose of this study was to examine whether routine blood tests can be useful in predicting mortality in COPD patients. METHODS: Eligible studies were found through a search conducted in the PubMed and Embase databases, the Cochrane Library, and the Web of Knowledge. Twelve studies were included for the meta-analysis of five biochemical markers. Pooled odds ratios (ORs), matching 95% confidence intervals (CIs), and p-values for each of the biochemical markers were calculated using the random effect model. RESULTS: The following four examined biochemical markers were shown to be associated with mortality in patients suffering from COPD: anemia (OR=2.62, 95% CI: 1.60; 4.29, p=0.01), hypoalbuminemia (OR=2.90, 95% CI: 1.56; 5.40, p=0.0008), elevated NT-proBNP (OR=7.54, 95% CI: 4.04; 14.10, p<0.00001), and elevated cardiac troponin T (OR=3.10, 95% CI: 1.11; 8.25, p=0.03). hs-CRP was not found to be associated with increased mortality. CONCLUSION: In this study, we found that anemia, hypoalbuminemia, elevated NT-proBNP, and elevated cardiac troponin T were associated with increased mortality in patients suffering from COPD.

The effect of aromatase inhibitors on bone metabolism.

Aromatase inhibitors increase the disease-free survival in patients with receptor-positive breast cancer. Aromatase is a cytochrome P450 enzyme complex catalysing the conversion of androgens to oestrogens. These properties cause a significant increase in bone loss. In this MiniReview, we present data from the aromatase inhibitor studies and the studies designed to investigate aromatase inhibitor effect on bone metabolism. At the cellular level, oestrogen has profound effects on both osteoblasts and osteoclasts. Oestrogen decreases the osteoblastic production of resorptive cytokines and simultaneously increases the production of antireceptive cytokines, which leads to increased osteoclastic apoptosis and increased osteoblastic activity. Aromatase inhibitors inhibit the endogenous production of oestrogen by 50-90%. Studies designed to look at the effect of aromatase inhibitors on bone mineral density have shown a significant decrease in bone mineral density of the femoral neck in the aromatase inhibitor groups compared to placebo groups. Placebo-controlled studies lack statistical power to detect changes in fracture incidence; however, aromatase inhibitors increase the incidence of fractures in comparison with tamoxifen. We conclude that treatment with aromatase inhibitors leads to an increased bone loss and thus an increase in the risk of fractures in women with breast cancer.

Adverse bone effects during pharmacological breast cancer therapy.

The improved survival and cure rate of breast cancer patients leads to increased diagnosis of later occurring side effects to therapy such as osteoporosis. Conventional chemotherapies such as CMF and CEF are known to induce premature menopause, which increases bone loss but these therapies have additional detrimental effects on bone. The loss in bone mass during chemotherapy is substantial and may lead to increased fracture risk. The influence of taxanes on bone is less well known. Whereas tamoxifen has a slight protective effect on bone loss the opposite is true for aromatase inhibitors. Adverse effect reportings show, that adjuvant treatment with aromatase inhibitors in postmenopausal women increases the risk of clinical fractures as compared to tamoxifen. The Danish Bone Society suggests that all women with operable breast cancer have their fracture risk evaluated including a BMD measurement prior to initiation of adjuvant aromatase inhibitor therapy as a part of the standard examination program. If osteoporosis is diagnosed, anti-osteoporosis therapies should be considered. Moreover, all women undergoing adjuvant chemotherapy and endocrine therapy should be informed of the risk of bone loss and should receive life style advice of how to preserve bone. Adjuvant regimens in breast cancer patients improve survival and cure rates. Therefore it is preferable to use such therapies although they increase risk of side effects such as osteoporosis.

[Effect of aromatase inhibitors on bone metabolism]. / Effekten af aromatasehaemmere på knoglemetabolismen.

Aromatase inhibitors (AI) increase the disease-free survival of patients with receptor-positive breast cancer. They inhibit the endogenous production of estrogen by 50-90% and, in contrast to tamoxifen, reduce bone mineral density. Placebo-controlled studies have lacked statistical power to detect changes in fracture incidence; however, AI increases the incidence of fractures in comparison with tamoxifen. Therefore, we suggest that post-menopausal women starting on AI should be offered a DXA scan and that antiresorptive therapy should be considered for those with osteoporosis.

Fetal exposure to pimozide: a case report.

BACKGROUND: Pimozide is an antidopaminergic, antipsychotic drug. Exposure during human pregnancy has not been reported previously, and recommendations on its use are based on extrapolation from other antipsychotics with antidopaminergic activity. CASE: A 26-year-old woman had Gilles de la Tourette syndrome and obsessive-compulsive disorder. It was not possible to discontinue pimozide during pregnancy, although the dosage was reduced to 1 mg daily. In addition, she was treated with 20 mg fluoxetine until gestational week 27. By request of the patient, elective cesarean section was scheduled for week 38. As a precaution, pimozide was withdrawn 2 weeks prior to the section. During this period the patient's symptoms severely intensified, and an emergency cesarean section had to be performed at 36 weeks. A healthy male infant weighing 2,448 g was delivered. Pediatric examination of the infant and electroencephalogram demonstrated no neurologic abnormalities. On day 4 both mother and infant were discharged. CONCLUSION: This is the first published report on fetal exposure to pimozide.

Associated response in bone and lipids during hormone replacement therapy.

OBJECTIVE: In postmenopausal women, we investigated if the response in bone mineral density (BMD) was associated with the response in the atherogenic lipid profile during hormone replacement therapy. METHODS: We performed an exploratory, post-hoc analysis of data from a prospective double-blind placebo-controlled trial. Healthy postmenopausal women were randomised into five groups, each receiving different combinations of 17 beta-estradiol and gestodene or placebo. A total of 133 women completed the study. The study period was 3 years. The response in bone mass was expressed as the percentage change in BMD from baseline calculated by linear regression from semi-annual measurements. The change in lipid profile was evaluated as the average of three mid-cycle and end-cycle values in percentage from baseline in order to account for cyclic changes during sequential hormone therapy. RESULTS: A significant correlation between the increase in BMD of the spine and hip and forearm with the decrease in serum low density lipoprotein (LDL) and cholesterol was found. Additionally, the decrease in atherogenic lipids correlated significantly with the response in biochemical bone markers for resorption and formation. CONCLUSION: In conclusion, our study shows that it is the same women who have a favourable response in BMD as in the lipid-profile during hormone replacement therapy (HRT). The association is most likely driven by a common response in FSH to exogenous estradiol therapy. This indicates that common denominators for the response to HRT exist. Further studies are needed to explore and identify such predictors.